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Evaluation of the role of cortisol in modulating seasonal changes in immunity

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TitleInfo
Title
Evaluation of the role of cortisol in modulating seasonal changes in immunity
Name (type = personal)
NamePart (type = family)
Pierre
NamePart (type = given)
Kamau
NamePart (type = date)
1987-
DisplayForm
Kamau Pierre
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Androulakis
NamePart (type = given)
Ioannis P
DisplayForm
Ioannis P Androulakis
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Hacihaliloglu
NamePart (type = given)
Ilker
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Ilker Hacihaliloglu
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Shinbrot
NamePart (type = given)
Troy
DisplayForm
Troy Shinbrot
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Schlesinger
NamePart (type = given)
Naomi
DisplayForm
Naomi Schlesinger
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
outside member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
School of Graduate Studies
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (qualifier = exact)
2017
DateOther (type = degree); (qualifier = exact)
2017-10
CopyrightDate (encoding = w3cdtf); (qualifier = exact)
2017
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
Inflammatory diseases such as asthma, rheumatoid arthritis (RA) and systemic vasculitis exhibit seasonality with higher prevalence and aggravated symptoms occurring during the winter months. Though the underlying causes remain to be elucidated, disease seasonality has been associated with circannual changes in antibodies, hormonal levels, acute phase reactants and numerous immunomodulatory components. For instance, RA risk biomarkers such as IL-6R mRNA, sIL-6 receptor and C-reactive proteins vary significantly throughout the year with peak expressions during the winter season. Apart from seasonal variation, the dynamics of functions such as cytokine production and hormone secretion display diurnal fluctuations that are entrained to the external 24-hour light/dark cycle. The light fraction of the light/dark cycle, or photoperiod, varies predictably throughout the year and is a robust environmental cue that synchronizes seasonal variations in neuroendocrine function. It is well established that cortisol, regulated via hypothalamic-pituitary-adrenal (HPA) axis activity and entrained to the external photoperiod, is a potent immunomodulator whose level varies seasonally. A detailed experimental analysis of the role of the HPA axis in regulating seasonal changes in immune function is lacking due to the complex network of biological interactions. In this work, we developed a semi-mechanistic mathematical model to evaluate cortisol’s role in modulating seasonal immunological plasticity. Our results indicate a shift from an anti- to a pro-inflammatory state as the seasons progress from summer through winter with elevated expression of the cortisol-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), an inflammatory disease biomarker, predicted for the winter season. Experimentally, the pro-inflammatory phenotype correlated with mitotic asynchrony is mitigated following glucocorticoid-induced cell resynchronization. A cortisol-dependent, time-of-day and seasonal variability in the synchronization of the molecular clock and cell cycle was predicted. These findings have major health implications as the misalignment of internal dynamics with environmental signals has been associated with inflammatory disease progression. The current model provides a framework for exploring the impact of asynchrony between the circadian and cell cycle oscillators, amongst cells in a population, on immune system dynamics. Knowledge of the underlying putative mechanisms governing seasonal and diurnal modifications of immune system dynamics can be applied to design more effective preventative and chronotherapeutic strategies addressing the development and advancement of a pro-inflammatory state.
Subject (authority = RUETD)
Topic
Biomedical Engineering
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_8215
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (x, 163 p. : ill.)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Subject (authority = ETD-LCSH)
Topic
Cortisol
Subject (authority = ETD-LCSH)
Topic
Immunity system
Note (type = statement of responsibility)
by Kamau Pierre
RelatedItem (type = host)
TitleInfo
Title
School of Graduate Studies Electronic Theses and Dissertations
Identifier (type = local)
rucore10001600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/T3RR22C1
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Pierre
GivenName
Kamau
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2017-05-19 15:52:08
AssociatedEntity
Name
Kamau Pierre
Role
Copyright holder
Affiliation
Rutgers University. School of Graduate Studies
AssociatedObject
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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Technical

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2017-06-07T11:30:13
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